The primary objective of this proposal is to make further progress towards an understanding of the function of somatostatin in the normal pancreas and in diabetes with the aid of a radioimmunoassay for somatostatin in tissues and biological fluids including blood. The factors influencing the secretion of somatostatin will be determined using as a model monolayer cultures of neonatal rat pancreas. The biosynthesis of somatostatin will also be studied in this model. The status of somatostatin secretion from the pancreas and gut in diabetes will be determined by measurement of somatostatin in hepatic portal and peripheral plasma of animal models of diabetes using our recently developed rat plasma RIA. The plasma assay will be applied for studying circulating somatostatin in human diabetes particularly to determine whether peripheral blood somatostatin is increased in juvenile onset diabetes and decreased in maturity type diabetes as suggested by our animal studies. The pathogenesis of the somatostatin changes as well as their effect on the pathophysiology of the diabetic state will be elucidated.